A reoccurri ng observation in the study of genes involved in reproduction is their rapid, adaptive divergence. We have demonstrated the rapid di vergence oft en genes involved in reproduction by analyses of rates and patterns of di verge nce between primates. The goal of this proposal is to initiate st ud ies of the levels and types of human single nucleot ide polymorph isms for genes involved in reproduction, which will lay the fo undation for future assoc iat ions studies in vestigating unexplained failed in vitro fert ilization. The high d ivergence of amino acid seq uence between species for reproductivc proteins raises the quest ion of whether amino acid polymorphi sms with in humans could contribute to infe rtility. T he fundamenta l hypothes is is that a missmatch ofspcrm egg recognition molecules may lower the p robability of succcssful fer tilizatio n, resu lting in fa ilure of ill ,Iitro fertilization tria ls. This would be analogous to matches in major-bi stocompatib ilitycomplex molecules necessary for successful skin grafts or matching blood types for transfu s ions. Other animals (internal and external fert ilizers) exhibit extreme variation in the ability of males to successfully fert il ize fema les, which has been shown to be dependent upon both male and female genotype. Thi s characterization of polymorphi sm leve ls within humans at reproductive loci may prov ide insight into some cases on unexplained inferti lity, which accounts for approximately 10% of fa iled in vitro fe l1 ilization tria ls. "Unexplained infe rtil ity"'are cases where sperm and eggs appear nonnal, but fert ilizat ion fa ils for unknown reasons. This proposal aims to in vestigate the ge netic bas is for unexplai ned infertility.